Frailty prevalence in 42 European countries by age and gender: development of the SHARE Frailty Atlas for Europe.

Comparative frailty prevalence data across European countries is sparse due to heterogeneous measurement methods. The Survey of Health, Ageing and Retirement (SHARE) initiative conducted interviews with probability sampling of non-institutionalized elderly people in several European countries. Previous frailty analyses of SHARE datasets were limited to initial SHARE countries and did not provide age- and gender-stratified frailty prevalence. Our aim was to provide age- and gender-stratified frailty prevalence estimates in all European countries, with predictions where necessary. From 29 SHARE participating countries, 311,915 individual surveys were analyzed. Frailty prevalence was estimated by country and gender in 5-year age bands using the SHARE Frailty Instrument and a frailty index. Association of frailty prevalence with age, gender, and GDP per capita (country-specific economic indicator for predictions) was investigated in multivariate mixed logistic regression models with or without multiple imputation. Female gender and increasing age were significantly associated with higher frailty prevalence. Higher GDP per capita, with or without purchasing power parity adjustment, was significantly associated with lower frailty prevalence in the 65-79 age groups in all analyses. Observed and predicted data on frailty rates by country are provided in the interactive SHARE Frailty Atlas for Europe. Our study provides age- and gender-stratified frailty prevalence estimates for all European countries, revealing remarkable between-country heterogeneity. Higher frailty prevalence is strongly associated with lower GDP per capita, underlining the importance of investigating transferability of evidence across countries at different developmental levels and calling for improved policies to reduce inequity in risk of developing frailty across European countries.

Improved survival of non-small cell lung cancer patients after introducing patient navigation: A retrospective cohort study with propensity score weighted historic control.

OnkoNetwork is a patient navigation program established in the Moritz Kaposi General Hospital to improve the timeliness and completeness of cancer investigations and treatment. The H2020 SELFIE consortium selected OnkoNetwork as a promising integrated care initiative in Hungary and conducted a multicriteria decision analysis based on health, patient experience, and cost outcomes. In this paper, a more detailed analysis of clinical impacts is provided in the largest subgroup, non-small cell lung cancer (NSCLC) patients. A retrospective cohort study was conducted, enrolling new cancer suspect patients with subsequently confirmed NSCLC in two annual periods, before and after OnkoNetwork implementation (control and intervention cohorts, respectively). To control for selection bias and confounding, baseline balance was improved via propensity score weighting. Overall survival was analyzed in univariate and multivariate weighted Cox regression models and the effect was further characterized in a counterfactual analysis. Our analysis included 123 intervention and 173 control NSCLC patients from early to advanced stage, with significant between-cohort baseline differences. The propensity score-based weighting resulted in good baseline balance. A large survival benefit was observed in the intervention cohort, and intervention was an independent predictor of longer survival in a multivariate analysis when all baseline characteristics were included (HR = 0.63, p = 0.039). When post-baseline variables were included in the model, belonging to the intervention cohort was not an independent predictor of survival, but the survival benefit was explained by slightly better stage distribution and ECOG status at treatment initiation, together with trends for broader use of PET-CT and higher resectability rate. In conclusion, patient navigation is a valuable tool to improve cancer outcomes by facilitating more timely and complete cancer diagnostics. Contradictory evidence in the literature may be explained by common sources of bias, including the wait-time paradox and adjustment to intermediate outcomes.

Human health risk-benefit assessment of fish and other seafood: a scoping review.

Fish and other seafood are important sources of nutrients, but they are also sources of chemical contaminants that may cause adverse health effects. This article aimed to identify existing risk-benefit assessments (RBA) of fish, shellfish, and other seafood, compare methodologies, discuss differences and commonalities in findings, and identify limitations and ways forward for future studies. We conducted a scoping review of the scientific literature of studies in all languages published from 2000 through April 2019. We identified 106 RBA of fish and other seafood across Europe, Asia, North America, Africa, and at the global level. Studies were heterogeneous in terms of types of fish and other seafood considered, beneficial and adverse compounds assessed, and overall methodology. Collected data showed that a diet consisting of a variety of lean and fatty fish and other seafood is recommended for the overall population and that women of childbearing age and children should limit the consumption of fish and other seafood types that have a high likelihood of contamination. Our review emphasizes the need for evidence-based, up-to-date, and harmonized approaches in RBA in general.

Modeling costs and benefits of the organized colorectal cancer screening programme and its potential future improvements in Hungary.

OBJECTIVE: The national population-based colorectal cancer screening programme in Hungary was initiated in December 2018. We aimed to evaluate the current programme and investigate the costs and benefits of potential future changes to overcome the low coverage of the target population. METHODS: We performed an economic evaluation from a healthcare payer perspective using an established micro-simulation model (Microsimulation Screening Analysis-Colon). We simulated costs and benefits of screening with fecal immunochemical test in the Hungarian population aged 50-100, investigating also the impact of potential future scenarios which were assumed to increase invitation coverage: improvement of the IT platform currently used by GPs or distributing the tests through pharmacies instead of GPs. RESULTS: The model predicted that the current screening programme could lead to 6.2% colorectal cancer mortality reduction between 2018 and 2050 compared to no screening. Even higher reductions, up to 16.6%, were estimated when tests were distributed through pharmacies and higher coverage was assumed. This change in the programme was estimated to require up to 26 million performed fecal immunochemical tests and 1 million colonoscopies for the simulated period. These future scenarios have acceptable cost-benefit ratios of €8000-€8700 per life-years gained depending on the assumed adherence of invited individuals. CONCLUSIONS: With its limitations, the current colorectal cancer screening programme in Hungary will have a modest impact on colorectal cancer mortality. Significant improvements in mortality reduction could be made at acceptable costs, if the tests were to be distributed by pharmacies allowing the entire target population to be invited.

Using informative prior based on expert opinion in Bayesian estimation of the transition probability matrix in Markov modelling-an example from the cost-effectiveness analysis of the treatment of patients with predominantly negative symptoms of schizophrenia with cariprazine.

BACKGROUND: When patient health state transition evidence is missing from clinical literature, analysts are inclined to make simple assumptions to complete the transition matrices within a health economic model. Our aim was to provide a solution for estimating transition matrices by the Bayesian statistical method within a health economic model when empirical evidence is lacking. METHODS: We used a previously published cost-effectiveness analysis of the use of cariprazine compared to that of risperidone in patients with predominantly negative symptoms of schizophrenia. We generated the treatment-specific state transition probability matrices in three different ways: (1) based only on the observed clinical trial data; (2) based on Bayesian estimation where prior transition probabilities came from experts' opinions; and (3) based on Bayesian estimation with vague prior transition probabilities (i.e., assigning equal prior probabilities to the missing transitions from one state to the others). For the second approach, we elicited Dirichlet prior distributions by three clinical experts. We compared the transition probability matrices and the incremental quality-adjusted life years (QALYs) across the three approaches. RESULTS: The estimates of the prior transition probabilities from the experts were feasible to obtain and showed considerable consistency with the clinical trial data. As expected, the estimated health benefit of the treatments was different when only the clinical trial data were considered (QALY difference 0.0260), its combination with the experts' beliefs were used in the economic model (QALY difference 0.0253), and when vague prior distributions were used (QALY difference 0.0243). CONCLUSIONS: Imputing zeros to missing transition probabilities in Markov models might be untenable from the clinical perspective and may result in inappropriate estimates. Bayesian statistics provides an appropriate framework for imputing missing values without making overly simple assumptions. Informative priors based on expert opinions might be more appropriate than vague priors.

Development of transferability guidance for integrated care models with special focus on Central and Eastern European countries.

AIM: To develop pragmatic recommendations for Central and Eastern European (CEE) policymakers about transferability assessment of integrated care models established in higher income European Union (EU) countries. METHODS: Draft recommendations were developed based on Horizon 2020-funded SELFIE project deliverables related to 17 promising integrated care models for multimorbid patients throughout Europe, as well as on an online survey among CEE stakeholders on the relevance of implementation barriers. Draft recommendations were discussed at the SELFIE transferability workshop and finalized together with 22 experts from 12 CEE countries. RESULTS: Thirteen transferability recommendations are provided in three areas. Feasibility of local implementation covers the identification and prioritization of implementation barriers and proposals for potential solutions. Performance measurement of potentially transferable models focuses on the selection of models with proven benefits and assurance of performance monitoring. Transferability of financing methods for integrated care explores the relevance of financing methodologies and planning of adequate initial and long-term financing. CONCLUSIONS: Implementation of international integrated care models cannot be recommended without evidence on its local feasibility or scientifically sound and locally relevant performance assessment in the country of origin. However, if the original financing method is not transferable to the target region, development of a locally relevant alternative financing method can be considered.

Implementation of palliative care consult Service in Hungary - integration barriers and facilitators.

BACKGROUND: The Palliative Care Consult Service (PCCS) programme was among the first initiations in Hungary to provide palliative care for patients admitted to hospital. The PCCS team provides palliative care for mainly cancer patients and their family members and manages the patient pathway after being discharged from the hospital. The service started in 2014 with 300-400 patient visits per year. The aim of this study is to give a comprehensive overview of the PCCS programme guided by a conceptual framework designed by SELFIE ("Sustainable intEgrated chronic care modeLs for multi-morbidity: delivery, FInancing, and performancE"), a Horizon2020 funded EU project and to identify the facilitators and barriers to its wider implementation. METHODS: PCCS has been selected by the SELFIE consortium for in-depth evaluation as one of the Hungarian integrated care models for persons with multi-morbidity. The qualitative analysis of the PCCS programme was based on available documents of the care provider and interviews with different stakeholders related to the programme. RESULTS: The integrated, multidisciplinary and patient-centred approach was well-received among the patients, family members and clinical departments, as verified by the increasing number of requests for consultations. As a result of the patient pathway management across providers (e.g. from inpatient care to homecare) a higher level of coordination could be achieved in the continuity of care for seriously-ill patients. The regulatory framework has only partially been established, policies to integrate care across organizations and sectors and adequate financial mechanism to support the enhancement and sustainability of the PCCS are still missing. CONCLUSIONS: The service integration of palliative care could be implemented successfully in an academic hospital in Hungary. However, the continuation and enhancement of the programme will require further evidence on the performance of the integrated model of palliative care and a more systematic approach particularly regarding the evaluation, financing and implementation process.

Planning, implementation and operation of a personalized patient management system for subjects with first suspect of cancer (OnkoNetwork): system description based on a qualitative study.

BACKGROUND: OnkoNetwork is a recently established integrated care model with a personalized pathway system to manage patients with first suspect of a solid tumour in secondary care, that evolved as a regional initiative in Hungary. The primary aim of OnkoNetwork is the improvement of clinical outcomes via timely access to quality assured and defragmented healthcare services. The Horizon 2020 funded SELFIE project has selected OnkoNetwork for in-depth qualitative and quantitative evaluation. The aim of this study was to provide a qualitative evaluation of OnkoNetwork along the six components of the SELFIE conceptual framework: 1) service delivery, 2) leadership and governance, 3) workforce, 4) financing, 5) technologies and medical products, and 6) information and research. METHODS: Analysis of published and grey programme documentation, followed by 20 semi-structured interviews with representatives of programme initiators, general and financial managers, involved physicians and non-physician professionals, patients and their informal caregivers. Transcripts of all interviews were analysed by Mayring's content analysis method by two independent researchers. RESULTS: This study yielded the first comprehensive description of the programme. OnkoNetwork is a blue dahila in Central and Eastern Europe, providing timely and quality-assured healthcare services for the target patients by personalized patient path monitoring and management in a financially sustainable manner without macro-level financing of its operation. Innovative professional roles were implemented for non-physicians and physicians, and a supporting information technology application was developed. CONCLUSIONS: This paper provides a systematic description of OnkoNetwork on the six components of the SELFIE conceptual framework for integrated care in multimorbidity to understand how and why OnkoNetwork was implemented and cares (better) for its patients. Because integrated care models are designed and adjusted to their specific local needs and context, those few successful and sustainable models that were established in Central and Eastern European countries represent important benchmarks for other initiatives in this region. Experience with OnkoNetwork during its planning, implementation and operation including the description of key success factors and barriers as perceived by various stakeholder groups, may support the development of further integrated care models especially in countries with similar economic status and healthcare settings.

Medical Nutrition Terminology and Regulations in the United States and Europe-A Scoping Review: Report of the ISPOR Nutrition Economics Special Interest Group.

BACKGROUND: The term medical nutrition (MN) refers to nutritional products used under medical supervision to manage disease- or condition-related dietary needs. Standardized MN definitions, aligned with regulatory definitions, are needed to facilitate outcomes research and economic evaluation of interventions with MN. OBJECTIVES: Ascertain how MN terms are defined, relevant regulations are applied, and to what extent MN is valued. METHODS: ISPOR's Nutrition Economics Special Interest Group conducted a scoping review of scientific literature on European and US MN terminology and regulations, published between January 2000 and August 2015, and pertinent professional and regulatory Web sites. Data were extracted, reviewed, and reconciled using two-person teams in a two-step process. The literature search was updated before manuscript completion. RESULTS: Of the initial 1687 literature abstracts and 222 Web sites identified, 459 records were included in the analysis, of which 308 used MN terms and 100 provided definitions. More than 13 primary disease groups as per International Classification of Disease, Revision 10 categories were included. The most frequently mentioned and defined terms were enteral nutrition and malnutrition. Less than 5% of the records referenced any MN regulation. The health economic impact of MN was rarely and insufficiently (n = 19 [4.1%]) assessed, although an increase in economic analyses was observed. CONCLUSIONS: MN terminology is not consistently defined, relevant European and US regulations are rarely cited, and economic evaluations are infrequently conducted. We recommend adopting consensus MN terms and definitions, for example, the European Society for Clinical Nutrition and Metabolism consensus guideline 2017, as a foundation for developing reliable and standardized medical nutrition economic methodologies.

Prostaglandin F2alpha potentiates the calcium dependent activation of mitochondrial metabolism in luteal cells.

Cytoplasmic Ca2+ signals are transferred to the mitochondria and activate the Krebs cycle. We have compared the efficiency of this process for two Ca2+ mobilising agonists, PGF2alpha and ATP (acting at metabotropic P2 receptors) in rat luteal cells. [Ca2+]c, [Ca2+]m and mitochondrial NAD(P)H were monitored by means of microspectrofluorimetry and confocal microscopy. While both agonists caused similar elevations of [Ca2+]c, changes in NAD(P)H were larger in response to PGF2alpha than to ATP. PGF2alpha more effectively increased NAD(P)H level also in mouse luteal cells. PGF2alpha caused a faster rate of rise of NAD(P)H fluorescence than ATP when reoxidation was prevented with rotenone, suggesting a faster rate of NAD(P)+ reduction. The NAD(P)H response to both agonists was dependent on the mobilisation of stored Ca2+. We found no difference in the efficacy of transmission of the [Ca2+]c signal to mitochondria in response to PGF2alpha and ATP. Raising [Ca2+]c with ionomycin increased the NAD(P)H signal, which was further raised by PGF2alpha but not by ATP. These data suggest that PGF2alpha potentiates the Ca2+-induced stimulation of mitochondrial metabolism by a Ca2+-independent mechanism and shows that agonists may modulate mitochondrial function differentially through a novel process beyond the simple transfer of Ca2+ from ER to mitochondria.

The effect of cytoplasmic Ca2+ signal on the redox state of mitochondrial pyridine nucleotides.

As first observed in rat adrenal glomerulosa cells, cytoplasmic Ca(2+) signal, induced by K(+), angiotensin II or vasopressin, evokes an increase in the level of reduced mitochondrial pyridine nucleotides, NADH and NADPH. Prostaglandin F(2)alpha and extracellular ATP exert similar effects in rat ovarian luteal cells. This coupling of cytoplasmic Ca(2+) concentration and mitochondrial metabolism occurs also when the stimuli are applied at physiological concentration and under conditions when no formation of high-Ca(2+) perimitochondrial microdomains may be presumed. We present evidence that low submicromolar Ca(2+) signals in the cytoplasm can increase mitochondrial Ca(2+) concentration and activate mitochondrial dehydrogenation processes. Several observations support the assumption that intramitochondrial Ca(2+) signals play a significant role in the stimulation of steroid hormone production.